Papillomavirus chimeric protein and application thereof

Abstract

Provided is a papillomavirus chimeric protein, the skeleton thereof being a papillomavirus L1 protein or a mutant thereof, at least one human papillomavirus 33-type L2 protein or mutant polypeptide thereof being embedded on the skeleton. The present papillomavirus chimeric protein can be used for preparing a vaccine for preventing papillomavirus infections and infection induced disease.

What is claimed is: 
     
       1. A chimeric papillomavirus protein, comprising: a papillomavirus HPV16 L1 protein or a mutant of the papillomavirus HPV16 L1 protein as a scaffold; and at least one polypeptide from a HPV33 L2 protein or from a mutant of the HFV33 L2 protein inserted into the scaffold, wherein
 the at least one polypeptide is shown as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, or SEQ ID NO: 6, 
 the at least one polypeptide is inserted into a surface region of the HPV16 L1 protein or the mutant of the HPV16 L1 protein, and 
 the at least one polypeptide is selected from the group consisting of: 
 the polypeptide from the HPV33 L2 protein shown as SEQ ID NO: 1 or SEQ ID NO: 2 is inserted into the HPV16 L1 protein or the mutant of the HPV16 L1 protein between amino acid positions 136 and 137, 
 after deletion of amino acid 135-138 region from the HPV16 L1 protein or the mutant of the HPV16 L1 protein, the polypeptide from the HPV33 L2 protein shown as SEQ ID NO: 5 or SEQ ID NO: 6 is inserted into the HPV16 L1 protein or the mutant of the HPV16 L1 protein between amino acid positions 134 and 139, and 
 after deletion of amino acid 431-432 region from the HPV16 L1 protein or the mutant of the HPV16 L1 protein, the polypeptide from the HPV33 L2 protein shown as SEQ ID NO: 2 or SEQ ID NO: 3 is inserted into the HPV16 L1 protein or the mutant of the HPV16 L1 protein between amino acid positions 430 and 433. 
 
     
     
       2. The chimeric papillomavirus protein according to  claim 1 , wherein the HPV16 L1 protein or the mutant of the HPV16 L1 protein is shown as SEQ ID NO: 4 or the amino acid sequence of SEQ ID NO: 4 with 31 amino acid deletion at the C-terminus. 
     
     
       3. A polynucleotide encoding the chimeric papillomavirus protein according to  claim 1 . 
     
     
       4. A polymer composed of papillomavirus capsid protein, wherein the polymer is a chimeric pentamer or chimeric virus-like particle, which contains the chimeric papillomavirus protein of  claim 1  or is consisted of the chimeric papillomavirus protein of  claim 1 . 
     
     
       5. A method for preventing HPV infection or HPV infection-associated diseases, comprising administering a prophylactically effective amount of the chimeric papillomavirus protein of one of  claims 1  and  2  or the chimeric pentamer or chimeric virus-like particle of  claim 4  to a subject. 
     
     
       6. A vaccine for preventing papillomavirus infection or infection-associated diseases, comprising the polymer of  claim 4 , adjuvants, and excipients or vehicles for the vaccine. 
     
     
       7. The polynucleotide of  claim 3 , wherein the sequence of the polynucleotide is optimized according to the codon usage preference of  E. coli  or insect cells. 
     
     
       8. The vaccine of  claim 6 , further comprising at least one virus-like particle or chimeric virus-like particle derived from mucosal and/or cutaneous HPV. 
     
     
       9. The vaccine of  claim 6 , wherein the adjuvant is a human adjuvant. 
     
     
       10. The vaccine of  claim 9 , wherein the human adjuvant is a composition selected from the group consisting of: a composition comprising Alum adjuvant, oil-in-water emulsion or water-in-oil emulsion and TLR agonist, a composition comprising aluminum hydroxide adjuvant or aluminum phosphate adjuvant, polyinosinic-polycytidic acid adjuvant and stabilizing agent, and a composition comprising MF59 adjuvant, polyinosinic-polycytidic acid adjuvant and stabilizing agent. 
     
     
       11. A vector comprising the polynucleotide of  claim 3  or  claim 7 . 
     
     
       12. An isolated host cell comprising the vector of  claim 11 .